Wortmannin

  • (1R, 3R, 5S, 9R, 18S ) -18 - ( methoxymethyl ) -1,5 -dimethyl- 6,11,16 - trioxo -13 ,17- dioxapentacyclo [ 10.6.1.0 ^ { 2,10 } .0 ^ { 5,9 } .0 ^ { 15,19 }] - nonadeca -2 ( 10) 12 ( 19) ,14- triene-3 - yl acetate (IUPAC)
  • KY 12420

Crystalline solid

240 ° C

Risk

  • 4 mg · kg -1 ( LD50, rat, oral)
  • 18 mg · kg -1 ( LD50, mouse, ip)

Template: Infobox chemical / molecular formula search available

Wortmannin is a mycotoxin. The compound is named after the German mycologist Julius Wortmann.

Occurrence

Wortmannin is of colonies of fungi Fusarium oxysporum, Fusarium avenaceum, Fusarium sambucinum, and the hose fungus Penicillium funiculosum formed, from which it can be isolated.

Pharmacological action

Wortmannin has no antibacterial properties, but is a highly potent fungicide. It is also a highly potent PI3K inhibitor and was the first identified PI3K inhibitor. It binds it on the furan ring covalently attached to a lysine at position 802, the IC50 value was 30 nmol. Wortmannin also in higher concentrations in the position mTOR, DNA-dependent protein kinase ( DNA-PK ), phosphatidylinositol -4- kinase, myosin light - chain kinase and mitogen activated protein kinase ( MAP kinase ) to inhibit. It has a strong anti-inflammatory and immunosuppressive effect.

Disadvantage is the high liver toxicity of wortmannin, which is why the pure substance has not yet found clinical application. One way this undesirable side effect to suppress the conjugation of wortmannin to a monoclonal antibody.

PX -866 is a synthetically modified descendant of Wortmannins and as an experimental drug currently (as of June 2011) in three oncological phase II studies ( glioblastoma, colorectal carcinoma head and neck cancers. )

Further Reading

  • J. Wang, Y. Cai, Y. Miao, SK Lam, L. Jiang: Wortmannin induces homotypic fusion of plant prevacuolar compartments. In: Journal of experimental botany Volume 60, Number 11, 2009, pp. 3075-3083, ISSN 1460-2431. doi: 10.1093/jxb/erp136. PMID 19,436,047th PMC 2718212 (Free full text ).
  • L. Chu, I. Norota, K. Ishii, M. Endoh: Wortmannin Inhibits the increase enlarge in myofilament Ca ( 2 ) sensitivity induced by cross-talk of endothelin -1 in canine ventricular myocardium with norepinephrine. In: Journal of pharmacological sciences Volume 109, Number 2, February 2009, pp. 193-202, ISSN 1347-8613. PMID 19,234,363th
  • JW Lee, LV Roze, JE Linz: Evidence did a wortmannin - sensitive signal transduction pathway Regulates aflatoxin biosynthesis. In: Mycologia Volume 99, Number 4, 2007 Jul-Aug, pp. 562-568, ISSN 0027-5514. PMID 18,065,007th
  • Y. Liu, N. Jiang, J. Wu, W. Dai, JS Rosenblum: Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. In: The Journal of biological chemistry Volume 282, Number 4, December 2007, pp. 2505-2511, ISSN 0021-9258. doi: 10.1074/jbc.M609603200. PMID 17,135,248th
  • W. Kim, J. Seong, JH An, HJ Oh: Enhancement of tumor radio response by wortmannin in C3H/HeJ hepatocarcinoma. In: Journal of radiation research Volume 48, Number 3, May 2007, pp. 187-195, ISSN 0449-3060. PMID 17,435,377th
  • P. Wipf, RJ holder: Chemistry and biology of wortmannin. In: Organic & biomolecular chemistry Volume 3, Number 11, June 2005, pp. 2053-2061, ISSN 1477-0520. doi: 10.1039/b504418a. PMID 15,917,886th
CAS registry number PubChem Dangerous Substances Directive (67/548/EEC) Intraperitoneal injection Immunosuppression Glioblastoma multiforme Digital Object Identifier Immunopharmacology and Immunotoxicology International Journal of Cancer
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